Does anyone know if there might be a positive connection between the clearing of amyloid beta proteins in mice with Alzheimers and clearing of Lewy Body clumps in LBD patients? I wonder if this new finding will relate from Alzheimers over to LBD since many current Alz meds work better for many LBD patients.

For those who have not heard, in the past few days it was announced that scientists found that mice genetically altered to have Alz experienced a rapid and significant washing away of the amyloid beta in their brains and apparent reversal of the disease. Bexarotene is currently available and ADA approved for skin cancer treatment. Trials are set to begin within weeks to see if humans respond like mice did, find appropriate dosage levels, safety, etc.This is the second significant finding in about two weeks concerning Alzheimers. Does this translate to LBD?

_________________Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.

Gary Landreth, one of the authors of Thursday's Science paper and a professor of neurosciences at Case Western Reserve University in Cleveland, said he expected to begin a safety study in 12 healthy patients next month, but there weren't any current plans for a larger clinical trial. He said he has received a "massive response" from patients or families but that caution is needed because the work is so preliminary.

Thu Feb 16, 2012 12:43 am

Pat

Joined: Sun Jun 24, 2007 5:35 pmPosts: 349

Re: Connection of bexarotene treatment and LBD?

Robin, I made the statement based on what was said in the original article I read--that 12 folks would be used as a small sample group in late Feb or early March. Those results should be available about 4 months after the testing begins, according to the article. But I cannot find that particular article right now--it is several days old.Here are a couple of articles for everyone to read who might be interested. These appear more cautious than the first one I read. There was a big scrambling of patients and caregivers when the first article came out--folks wanting to know how to get it off label from their doctors.

Probably just a matter of semantics. A "safety study" with 12 participants is not considered a "trial."

Thu Feb 16, 2012 4:09 pm

labeckett

Joined: Thu Apr 21, 2011 9:07 pmPosts: 248

Re: Connection of bexarotene treatment and LBD?

The safety study sounds very much like a Phase I study, which would assess whether the proposed dosage is safe in this patient population, and if not, whether a lower dosage would be safe. Usually people get a little bit of efficacy data, too, but it's considered very preliminary and just helps to justify a larger, typically Phase II study. The Phase II study does look at efficacy but they are usually not randomized comparative studies, just something that says: if it looks great, let's go to a big randomized study, that is, Phase III. If nothing good happens, let's move on to another drug. If it's in between, we have to think harder to decide.

If the study gets registered with clinicaltrials.gov, it should be possible to find out more. It's not registered yet, at least not on the web site yet.

The most likely organizer nationally would be the Alzheimer's Clinical Trials Center at UC San Diego, working with the national Alzheimer's Disease Centers, though a Phase I trial might be done locally at Case Western. Since the primary impact in mice was on amyloid clearance, I assume they would use amyloid imaging, for example PiB or AV45 PET imaging, as the initial biomarker outcome. If I were designing such a study, I might look to recruit people who already had amyloid imaging, for example, participants in the ADNI study, so you wouldn't have to do as much screening to ensure amyloid-positivity and to have a sense of baseline cognitive function. I haven't heard of such plans yet, either through ADNI or through the ADC's.

I don't know enough about it to have any idea whether it would have an effect on synuclein or Lewy bodies. There are other drugs with similar mechanisms of action that are being mentioned as possible alternatives to bexarotene.

The Scientific American article (which I agree is the best of the bunch) says that the first study in humans will be led by a private company:

"Landreth and Cramer ... have formed a company called ReXceptor Therapeutics that intends to begin a preliminary trial in humans in the next few months to determine whether the drug crosses the bloodâbrain barrier and clears amyloid, as it does in mice. If those processes occur, clinical trials on the drug's effectiveness in humans could begin even this year, and they would probably last from 18 months to three years. The drug loses patent protection for cancer this year, but Case Western has filed for patents for its use in Alzheimer's."

I think they only way they could determine clearance of amyloid is to use PiB imaging, as you suggest, Laurel.

Thu Feb 16, 2012 10:55 pm

Pat

Joined: Sun Jun 24, 2007 5:35 pmPosts: 349

Re: Connection of bexarotene treatment and LBD?

Laurel, what is your background? You seem to have an understanding of how research procedures work.Pat

Robin, thanks for clarifying the status of human trials for everyone reading this thread. All of us are hoping this can work and soon.Off label cost of this drug, if you could get it, is prohibitive for most folks.Pat

Personally, I think it would be unethical at this time for an MD to write an RX for bexarotene for someone with a clinical DX of AD. Many AD families are desperate, of course.

Fri Feb 17, 2012 12:19 pm

labeckett

Joined: Thu Apr 21, 2011 9:07 pmPosts: 248

Re: Connection of bexarotene treatment and LBD?

Hi Robin,It does seem as if it would be very questionable to write a scrip for bexarotene off-label for AD!

Here is one thought: it's approved as second-line therapy for cutaneous t-cell lymphoma, and under study for other cancers. Since many cancer patients are elderly, I have to wonder if anyone is scouting around for t-cell lymphoma patients who also have AD. Seems like this might be acceptable to an IRB, if you could find such patients (or those in clinical trials for other cancers.) I looked up clinical trials for bexarotene on clinical trials.gov and found most of the active ones, that are still recruiting, are for leukemia or lymphoma. But there are some with unknown status for lung cancer and metastatic breast cancer.

Pat - I have a PhD in statistics from Stanford, and am currently head of a med school division of biostatistics, and head of biostatistics for our cancer center and Alzheimer's Disease Center (for last 11 years). I'm also head of the national core for the Alzheimer's DIsease Neuroimaging Initiative (ADNI). I've been doing collaborative medical research for many years, including a long-time focus on Alzheimer's, and a lot of clinical trials work (though more in HIV and cancer than AD). So I'm not a clinician but I spend a lot of time designing and carrying out clinical and epidemiological research, and also a lot of time as a reviewer. It's a big help in some ways in caring for my parents because of access to expert colleagues, as well as my own background and experience with the medical literature. But at the end of the day, we are all still confronting a disease with few good answers long term and many demands on caregivers, and the practical knowledge you folks are kind enough to share is a huge help! And if any of this background is helpful to other folks, that's a good thing, too. (I'm really grateful to Robin for the time she spends keeping track of news and posting and commenting - there's no way I could do that now - it's about all I can do to look in very so often and see if I can add anything useful.)

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